title: Synthesis of chromone carboxamide derivatives with antioxidative and calpain inhibitory properties.
abstract: The overactivation of μ-calpain can cause serious cell damage in several diseases. Furthermore, cell death in a number of neurodegenerative disorders is linked to the overproduction of reactive oxygen species. Therefore, antioxidants and μ-calpain inhibitors could have the therapeutic potentials to treat cell death related diseases. New chromone carboxamide derivatives 3 were synthesized to provide alternative μ-calpain inhibitors to compound 2, a conformationally constrained structural variant of MDL 28,170. Compounds 3h and 3l exhibited the most potent μ-calpain inhibitory activities (IC50=0.09-0.10 μM), and were comparable to 2 in this respect (IC50=0.07 μM). Compound 3i showed both potent μ-calpain inhibitory activity (IC50=0.28 μM) and antioxidant activities in DPPH scavenging and lipid peroxidation inhibition assays.
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong Dongdaemoon-ku, Seoul 130-701, Republic of Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Lee
authors.forename: Seo Yun
authors.initials: SY
authors.lastname: Jung
authors.forename: Hyoung Ja
authors.initials: HJ
authors.lastname: Kim
authors.forename: Changbae
authors.initials: C
authors.lastname: Jin
authors.forename: Yong Sup
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002867:Chromones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D002867:Chromones; D002154:Calpain